Integrative genomic and functional analysis of RAB3B in lung adenocarcinoma: associations with m6A modification and...

Lung adenocarcinoma (LUAD) is characterized by high mortality and recurrence. This study investigated the clinical significance and biological role of RAB3B as a potential biomarker in LUAD.

We analyzed The Cancer Genome Atlas and Gene Expression Omnibus datasets for RAB3B differential expression, prognosis, and correlation with clinical features. Immunohistochemistry validated RAB3B protein levels in tissues. qRT-PCR was employed to detect RAB3B mRNA expression in lung cancer cell lines and a normal bronchial epithelial cell line. Following shRNA-mediated knockdown of RAB3B, cell proliferation, colony formation, and migration were assessed via CCK-8, colony formation, and wound healing assays. Furthermore, we examined RAB3B's correlation with m6A regulatory genes and constructed a RAB3B-centric ceRNA network.

RAB3B was significantly overexpressed in LUAD tissues. High RAB3B levels correlated with pathological stages and male gender. In vitro, qRT-PCR confirmed that RAB3B mRNA expression was markedly upregulated in lung cancer cell lines. Furthermore, RAB3B protein levels were validated by IHC to be significantly higher in malignant tissues than in normal controls. Functional assays revealed that silencing RAB3B significantly inhibited the proliferation, colony formation, and migratory capacity of cancer cells. Additionally, RAB3B expression was positively correlated with the m6A "reader" gene IGF2BP3. A ceRNA network highlighted hsa-miR-15b-5p as a key downregulated miRNA targeting RAB3B, with several upregulated lncRNAs potentially sponging hsa-miR-15b-5p to enhance RAB3B expression.

RAB3B is a prognostic biomarker and promotes LUAD progression by enhancing cell proliferation and motility. This process likely involves IGF2BP3 and a miR-15b-5p-related ceRNA mechanism, highlighting RAB3B as a promising biomarker or candidate for further therapeutic study.